(2,4,4-trimethyl-1-cyclohexene)carbaldehyde (β-cyclolavandulal) has been isolated from caraway, Carum carvi Linn., grown in India and used as a folk medicine and from fungi as a secondary metabolite (Non-Patent Document 1).
The (2,4,4-trimethyl-1-cyclohexene)carbaldehyde (β-cyclolavandulal) is also known as a constituent of WS-9659A (lavanducyanine) and WS-9659B, which have been isolated from actinomycete Streptomyces as inhibitors of testosterone 5α-reductase (Non-Patent Document 2).
Vellutini et al. have isolated a total of eight compounds including (2,4,4-trimethyl-1-cyclohexenyl)methyl esters (general name: β-cyclolavandulyl esters) and 4,4,6-trimethyl-1-cyclohexenyl)methyl esters (general name: β-isocyclolavandulyl esters) from essential oils of leaves and roots of Peucedanum paniculatum Linn. grown in Corsica, and determined the structures thereof (Non-Patent Document 3).
Oda et al. have reported the syntheses of (2,4,4-trimethyl-1-cyclohexene)carbaldehyde (general name: β-cyclolavandulal) and (2,4,4-trimethyl-1-cyclohexene)methanol (general name: β-cyclolavandulol) from 3,3-dimethylcyclohexanone as a starting material. In the syntheses, 3,3-dimethylcyclohexanone was subjected to methoxycarbonylation to obtain a ketoester; the ketoester was converted into an enol phosphate derivative; then a methyl group was introduced thereto with dimethyllithium cuprate; the resulting product was reduced with lithium aluminum hydride to obtain the (2,4,4-trimethyl-1-cyclohexene)methanol; and the (2,4,4-trimethyl-1-cyclohexene)methanol was oxidized with pyridinium chlorochromate (PCC) to obtain (2,4,4-trimethyl-1-cyclohexene)carbaldehyde (Non-Patent Document 4).
Kinoshita et al. have reported the synthesis of (2,4,4-trimethyl-1-cyclohexene)methanol as a synthetic intermediate of WS-9659A (lavanducyanine) by using 3,3-dimethylglutaric anhydride as a starting material in an overall yield of 33%. The synthesis includes five steps of reduction into a lactone, conversion with methyllithium into a methyl hemiacetal, conversion with iodine into a keto iodide, alkylation and condensation with trimethyl phosphonoacetate, and reduction with diisobutylaluminum into the allyl alcohol (Non-Patent Document 5).
Gandhi et al. have reported the synthesis of (2,4,4-trimethyl-1-cyclohexene)carbaldehyde (Non-Patent Document 6). According to the abstract, 3,3-dimethylcyclohexanone as a raw material was reached with ethyl formate for condensation to obtain 3,3-dimethyl-6-(hydroxymethylene)cyclohexanone, and then the 3,3-dimethyl-6-(hydroxymethylene)cyclohexanone was reacted with isobutyl alcohol under an acidic condition to obtain a corresponding isobutoxymethylene derivative in a yield of 61%. The isobutoxymethylene derivative further was treated with methylmagnesium iodide, and hydrolyzed with dilute sulfuric acid to obtain the target compound in a yield of 66%.
(2,4,4-Trimethyl-2-cyclohexenyl)methyl butyrate ester [another name: (2,4,4-trimethyl-2-cyclohexenyl)methyl n-butyrate, cyclolavandulyl butyrate] has been isolated as an attractant of an important parasitic wasp in controlling mealybugs. More specifically, Tabata et al. have found (2,4,4-trimethyl-2-cyclohexenyl)methyl butyrate ester, which is a substance attracting Anagyrus sawadai that is one of the wasps living parasitically with the mealybug, from by-products generated when lavandulol is treated with butyryl chloride to synthesize lavandulyl butyrate, have isolated the active substance, and have determined the structure thereof (Non-Patent Document 7). The lavandulol as the starting material was treated with butyryl chloride to obtain (2,4,4-trimethyl-2-cyclohexenyl)methyl butyrate ester in a yield of 1.2%. (2,4,4-Trimethyl-1-cyclohexenyl)methyl butyrate ester, which is a regioisomer of the (2,4,4-trimethyl-2-cyclohexenyl)methyl butyrate ester with respect to the position of a double bond, is similar to 2-isopropylidene-5-methyl-4-hexen-1-yl butyrate ester (fujikonyl butyrate, Non-Patent Document 8), which is known as a sex pheromone of Planococcus kraunhiae, with respect to the position of a double bond from a polar group and has attracted attention due to attractive activities to parasitic wasps.